Sensory Afferent Renal Nerve Activated Gαi2 Subunit Proteins Mediate the Natriuretic, Sympathoinhibitory and Normotensive Responses to Peripheral Sodium Challenges

Jesse D Moreira; Kayla M Nist; Casey Y Carmichael; Jill T Kuwabara; Richard D Wainford

doi:10.3389/fphys.2021.771167

Sensory Afferent Renal Nerve Activated Gαi₂ Subunit Proteins Mediate the Natriuretic, Sympathoinhibitory and Normotensive Responses to Peripheral Sodium Challenges

Front Physiol. 2021 Nov 30:12:771167. doi: 10.3389/fphys.2021.771167. eCollection 2021.

Authors

Jesse D Moreira^{1

2}, Kayla M Nist^{1

3}, Casey Y Carmichael^{1

4}, Jill T Kuwabara^{1

4}, Richard D Wainford^{1

4}

Affiliations

¹ Whitaker Cardiovascular Institute, School of Medicine, Boston University, Boston, MA, United States.
² Department of Medicine, School of Medicine, Boston University, Boston, MA, United States.
³ Department of Anatomy & Neurobiology, School of Medicine, Boston University, Boston, MA, United States.
⁴ Department of Pharmacology and Experimental Therapeutics, School of Medicine, Boston University, Boston, MA, United States.

Abstract

We have previously reported that brain Gαi₂ subunit proteins are required to maintain sodium homeostasis and are endogenously upregulated in the hypothalamic paraventricular nucleus (PVN) in response to increased dietary salt intake to maintain a salt resistant phenotype in rats. However, the origin of the signal that drives the endogenous activation and up-regulation of PVN Gαi₂ subunit protein signal transduction pathways is unknown. By central oligodeoxynucleotide (ODN) administration we show that the pressor responses to central acute administration and central infusion of sodium chloride occur independently of brain Gαi₂ protein pathways. In response to an acute volume expansion, we demonstrate, via the use of selective afferent renal denervation (ADNX) and anteroventral third ventricle (AV3V) lesions, that the sensory afferent renal nerves, but not the sodium sensitive AV3V region, are mechanistically involved in Gαi₂ protein mediated natriuresis to an acute volume expansion [peak natriuresis (μeq/min) sham AV3V: 43 ± 4 vs. AV3V 45 ± 4 vs. AV3V + Gαi₂ ODN 25 ± 4, p < 0.05; sham ADNX: 43 ± 4 vs. ADNX 23 ± 6, AV3V + Gαi₂ ODN 25 ± 3, p < 0.05]. Furthermore, in response to chronically elevated dietary sodium intake, endogenous up-regulation of PVN specific Gαi₂ proteins does not involve the AV3V region and is mediated by the sensory afferent renal nerves to counter the development of the salt sensitivity of blood pressure (MAP [mmHg] 4% NaCl; Sham ADNX 124 ± 4 vs. ADNX 145 ± 4, p < 0.05; Sham AV3V 125 ± 4 vs. AV3V 121 ± 5). Additionally, the development of the salt sensitivity of blood pressure following central ODN-mediated Gαi₂ protein down-regulation occurs independently of the actions of the brain angiotensin II type 1 receptor. Collectively, our data suggest that in response to alterations in whole body sodium the peripheral sensory afferent renal nerves, but not the central AV3V sodium sensitive region, evoke the up-regulation and activation of PVN Gαi₂ protein gated pathways to maintain a salt resistant phenotype. As such, both the sensory afferent renal nerves and PVN Gαi₂ protein gated pathways, represent potential targets for the treatment of the salt sensitivity of blood pressure.

Keywords: afferent renal sympathetic nerves; blood pressure; central Gαi2 proteins; natriuresis; sodium homeostasis.

Abstract

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